{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T09:59:15Z","timestamp":1792835955637,"version":"4.5.0"},"reference-count":47,"publisher":"National Academy of Sciences","issue":"9","license":[{"start":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T00:00:00Z","timestamp":1676937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,2,28]]},"abstract":"<jats:p>The aggregation of \u03b1-synuclein into amyloid fibrils has been under scrutiny in recent years because of its association with Parkinson\u2019s disease. This process can be triggered by a lipid-dependent nucleation process, and the resulting aggregates can proliferate through secondary nucleation under acidic pH conditions. It has also been recently reported that the aggregation of \u03b1-synuclein may follow an alternative pathway, which takes place within dense liquid condensates formed through phase separation. The microscopic mechanism of this process, however, remains to be clarified. Here, we used fluorescence-based assays to enable a kinetic analysis of the microscopic steps underlying the aggregation process of \u03b1-synuclein within liquid condensates. Our analysis shows that at pH 7.4, this process starts with spontaneous primary nucleation followed by rapid aggregate-dependent proliferation. Our results thus reveal the microscopic mechanism of \u03b1-synuclein aggregation within condensates through the accurate quantification of the kinetic rate constants for the appearance and proliferation of \u03b1-synuclein aggregates at physiological pH.<\/jats:p>","DOI":"10.1073\/pnas.2208792120","type":"journal-article","created":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T13:58:31Z","timestamp":1676987911000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":104,"title":["Spontaneous nucleation and fast aggregate-dependent proliferation of \u03b1-synuclein aggregates within liquid condensates at neutral pH"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4816-9852","authenticated-orcid":false,"given":"Samuel T.","family":"Dada","sequence":"first","affiliation":[{"name":"Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge, Cambridge CB2 1EW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2850-9135","authenticated-orcid":false,"given":"Maarten C.","family":"Hardenberg","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge, Cambridge CB2 1EW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zenon","family":"Toprakcioglu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge, Cambridge CB2 1EW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena K.","family":"Mrugalla","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge, Cambridge CB2 1EW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5980-2778","authenticated-orcid":false,"given":"Mariana P.","family":"Cali","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge, Cambridge CB2 1EW, UK"},{"name":"Department of Chemistry, Federal University of S\u00e3o Carlos, S\u00e3o Carlos, 13565-905 S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3994-7560","authenticated-orcid":false,"given":"Mollie O.","family":"McKeon","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge, Cambridge CB2 1EW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Klimont","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge, Cambridge CB2 1EW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6931-5041","authenticated-orcid":false,"given":"Thomas C. 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